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The Journal of Neuroscience, December 1, 2001, 21(23):9092-9100

Opioid Receptor Modulation of a Metabolically Sensitive Ion Channel in Rat Amygdala Neurons

Xueguang Chen, Hector G. Marrero, and Jonathan E. Freedman

Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115

We have used single-channel patch-clamp recordings to study opiate receptor effects on freshly dissociated neurons from the rat amygdalohippocampal area (also called the posterior nucleus of the amygdala), an output nucleus of the amygdala implicated in appetitive behaviors. Dissociated cells included a distinct subpopulation that was 30-40 µm in diameter, multipolar or pyramidal in shape, and immunoreactive for neuron-specific enolase, µ opioid receptors, and galanin. In whole-cell perforated-patch recordings, these cells responded to low concentrations of µ opioid agonists with a hyperpolarization. In cell-attached single channel recordings, these cells expressed a large variety of K+-permeable ion channels, including 20-100 pS inward rectifiers and 150-200 pS apparent Ca2+-activated K+ channels, none of which appeared sensitive to the presence of opioid drugs. In contrast, a 130 pS inwardly rectifying channel was selectively activated by µ opioid receptors in this same subpopulation of cells and was active only in the presence of opioid agonists, and inhibited in the presence of antagonists. Channels identical to the 130 pS channel in conductance and voltage sensitivity were activated in the absence of opioids, when the cells were treated with glucose-free medium or with the metabolic inhibitor rotenone. The sulfonylurea drug tolbutamide inhibited 130 pS channel openings elicited by opioids. Thus, a subpopulation of amygdala projection neurons expresses a metabolically sensitive ion channel that is selectively modulated by opiate receptors. This mechanism may allow opioid neurotransmitters to regulate ingestive behaviors, and thus, opiate drugs to influence reward pathways.

Key words: amygdala; patch-clamp; potassium channel; opiate receptor; opioid receptor; galanin; sulfonylurea; addiction; satiety


Copyright © 2001 Society for Neuroscience  0270-6474/01/21239092-09$05.00/0




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